Bioorganic and Medicinal Chemistry Letters 2005-Jun
4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na+/H+ exchanger isoform-1 (NHE-1) inhibitors.
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A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficacy. Especially the 4-nitro 20 and cyano 50 compounds excellently improved the cardiac function and reduced infarct size against ischemia/reperfusion injury.